AIDS is the most serious form of infection caused by The hiv. Thanks to advances in its treatment, today the disease has become chronic and Improve Life Quality of infected people. However, although antiretroviral therapy is effective in suppressing replication, the virus persists in reservoirs and recovers after discontinuation of therapy.
However, there are so-called post-treatment controllers, which maintain undetectable viral loads without taking medication, being a realistic model for functional HIV care. Other cases of cure are related to bone marrow transplantation or in rare patients who have defective viruses or genetic factors associated with a strong immune response to HIV from a type of lymphocyte, CD8+ T cells, in so-called elite controllers.
Now, researchers from the Hospital Clínic-IDIBAPS have presented during the World AIDS Conference 2022 an exceptional case of functional cure of AIDS, in which, although the virus is not completely eliminated from the body, the host’s immune system is able to control it without the need for drugs.
This is a patient who, after discontinuation of antiretroviral treatment, has absolute control of HIV replication, maintained for more than 15 years, with undetectable viral load without medication. Researchers from the University of Barcelona, the CIBER for Infectious Diseases (CIBERINFEC) and the Carlos III Health Institute have also participated in the work.
“The case is exceptional, not only because there are very few people with long-term post-treatment control, but also because of the mechanism of control of the virus, which is different from that described in elite controller patients and in other cases documented so far,” explains Josep. Mallolas, group leader at IDIBAPS and director of the Clinic’s HIV Unit.
For specialists, this episode sheds new light on the mechanisms by which certain people can control the virus after taking antiretroviral therapy.
In addition, it opens the door to the development of new potential treatment strategies to increase the activity of the cells involved in the innate response against the virus.
A unique case: 15 years of control
The study describes the immunological mechanisms of the patient, post-treatment controller, which have allowed her to maintain absolute dominance of virus replication for more than 15 years. The woman was diagnosed at the stage of acute HIV infection and was included in a clinical trial that prescribed two types of interventions: antiretroviral treatment for 9 months and various administrations of the immunosuppressant cyclosporine A (to improve the immune response).
“The patient did not have the classic genetic factors associated with HIV control and was not an elite controller of the disease,” says Josep M. Miró, group leader at IDIBAPS and specialist in infectious diseases at Hospital Clínic.
“Over these years we have found a pronounced and progressive drop in the number of viruses in its reservoir, which suggests control by the immune response,” explains Sonsoles Sanchez-Palomino, IDIBAPS researcher. On the other hand, the virus could be isolated and grown in the laboratory, indicating that it was not ‘defective’.
The researchers found that in cultures in vitro their blood cells were highly resistant to being infected by HIV, but that their purified CD4+ T cells were susceptible to infection. This suggests that other cell populations in the blood were blocking infection and could contribute to virus control.
Through a viral inhibition assay, the study has shown that there is a strong suppression of HIV promoted by two types of lymphocytes: ‘natural killer’ cells and CD8+ T lymphocytes. The former are part of the innate immune system and constitute the first line of defense against different pathogens; CD8+ T lymphocytes play a key role in the defense of cells against viruses and bacteria.
“The patient has very high levels of the two cells that could block HIV or destroy infected cells, thus achieving functional care,” says Núria Climent, IDIBAPS researcher. “The great novelty of this work is that we have characterized the cells that manage to control the virus,” she adds.
“Functional cure of HIV is a much more realistic goal on a larger scale than sterilizing cure—that is, complete elimination of all replication-competent viruses in infected patients—which is why it is so important to understand the underlying mechanisms,” he concludes. Juan Ambrosioni, doctor at the Clinic and researcher at IDIBAPS.